Developmental Inhibition of Gsk3 Rescues Behavioral and Neurophysiological Deficits in a Mouse Model of Schizophrenia Predisposition.
Neuron
; 89(5): 1100-9, 2016 Mar 02.
Article
em En
| MEDLINE
| ID: mdl-26898776
ABSTRACT
While the genetic basis of schizophrenia is increasingly well characterized, novel treatments will require establishing mechanistic relationships between specific risk genes and core phenotypes. Rare, highly penetrant risk genes such as the 22q11.2 microdeletion are promising in this regard. Df(16)A(+/-) mice, which carry a homologous microdeletion, have deficits in hippocampal-prefrontal connectivity that correlate with deficits in spatial working memory. These mice also have deficits in axonal development that are accompanied by dysregulated Gsk3ß signaling and can be rescued by Gsk3 antagonists. Here we show that developmental inhibition of Gsk3 rescues deficits in hippocampal-prefrontal connectivity, task-related neural activity, and spatial working memory behavior in Df(16)A(+/-) mice. Taken together, these results provide mechanistic insight into how the microdeletion results in cognitive deficits, and they suggest possible targets for novel therapies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Esquizofrenia
/
Predisposição Genética para Doença
/
Quinase 3 da Glicogênio Sintase
/
Modelos Animais de Doenças
/
Transtornos Mentais
/
Doenças do Sistema Nervoso
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article